This project is designed to identify atheroprotective effects of flaxseed oil. A mouse model of atherosclerosis, the B100+/+LDLr-/- mouse, will be studied to take advantage of similarities to humans in lipoprotein composition. The proposal is to directly compare flaxseed oil in diets providing 2% of energy as alpha-linolenic acid to a comparable diet containing enough fish oil to provide EPA+DHA as 2% of energy. Both of these diets will be compared to a diet containing saturated fat. Additional studies are proposed to find minimal effective levels of flaxseed oil required to demonstrate atheroprotection. All diets will contain 10% of energy as fat with no appreciable amounts of cholesterol added to the diets. We will examine diet-related differences in plasma lipid and lipoprotein metabolism, and we will study the diet response of liver lipid accumulation and secretion during recirculating perfusion. We will quantify the quality and extent of aortic atherosclerosis after 20 weeks of diet exposure. Based on preliminary data, we hypothesize that flaxseed oil will provide protection against development of atherosclerosis in spite of minimal effects on plasma lipid concentrations but significant effects on liver lipid compositions. We anticipate that flaxseed oil and fish oil-related differences in plasma lipoprotein composition will be identified that may predict decreased atherosclerosis. Further, we will examine macrophage inflammatory responses to the flaxseed oil and fish oil diets and detail mechanisms through which the ALA from flaxseed oil and EPA+DHA from fish oil could limit atherosclerosis.